Faculty Bibliography

OBJECTIVES/OBJECTIVE:To develop an assessment and recognition tool to identify elite athletes at risk for mental health symptoms and disorders. METHODS:We conducted narrative and systematic reviews about mental health symptoms and disorders in active and former elite athletes. The views of active and former elite athletes (N=360) on mental health symptoms in elite sports were retrieved through an electronic questionnaire. Our group identified the objective(s), target group(s) and approach of the mental health tools. For the assessment tool, we undertook a modified Delphi consensus process and used existing validated screening instruments. Both tools were compiled during two 2-day meeting. We also explored the appropriateness and preliminary reliability and validity of the assessment tool. SPORT MENTAL HEALTH ASSESSMENT TOOL 1 AND SPORT MENTAL HEALTH RECOGNITION TOOL 1: The International Olympic Committee Sport Mental Health Assessment Tool 1 (SMHAT-1) was developed for sports medicine physicians and other licensed/registered health professionals to assess elite athletes (defined as professional, Olympic, Paralympic or collegiate level; aged 16 years and older) potentially at risk for or already experiencing mental health symptoms and disorders. The SMHAT-1 consists of: (i) triage with an athlete-specific screening tool, (ii) six subsequent disorder-specific screening tools and (iii) a clinical assessment (and related management) by a sports medicine physician or licensed/registered mental health professional (eg, psychiatrist and psychologist). The International Olympic Committee Sport Mental Health Recognition Tool 1 (SMHRT-1) was developed for athletes and their entourage (eg, friends, fellow athletes, family and coaches). CONCLUSION/CONCLUSIONS:The SMHAT-1 and SMHRT-1 enable that mental health symptoms and disorders in elite athletes are recognised earlier than they otherwise would. These tools should facilitate the timely referral of those athletes in need for appropriate support and treatment.

The Non-Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non-motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross-validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health-related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non-motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomised clinical trials. Highlighting the prevalence and importance of non-motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non-motor symptoms in PD.

Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are learned without considering behavior. We develop preferential subspace identification (PSID), which is an algorithm that models neural activity while dissociating and prioritizing its behaviorally relevant dynamics. Modeling data in two monkeys performing three-dimensional reach and grasp tasks, PSID revealed that the behaviorally relevant dynamics are significantly lower-dimensional than otherwise implied. Moreover, PSID discovered distinct rotational dynamics that were more predictive of behavior. Furthermore, PSID more accurately learned behaviorally relevant dynamics for each joint and recording channel. Finally, modeling data in two monkeys performing saccades demonstrated the generalization of PSID across behaviors, brain regions and neural signal types. PSID provides a general new tool to reveal behaviorally relevant neural dynamics that can otherwise go unnoticed.

OBJECTIVE:To elucidate molecular risk factors for posterior segment uveitis using a functional genomics approach. DESIGN/METHODS:Genetic Association Cohort Study. METHODS:SETTING: Single-center study at an academic referral center. STUDY POPULATION/METHODS:164 patients with clinically diagnosed uveitis of the posterior segment. MAIN OUTCOME MEASURES/METHODS:Exome sequencing was used to detect variants identified in 164 patients with posterior segment uveitis. A phenotype-driven analysis, protein structural modeling and in silico calculations were then used to rank and predict the functional consequences of key variants. RESULTS:A total of 203 single nucleotide variants, in 23 genes across 164 patients, were included in this study. Both known and novel variants were identified in genes previously implicated in specific types of syndromic uveitis - such as NOD2 (Blau Syndrome) and CAPN5 NIV (Neovascular Inflammatory Vitreoretinopathy) - as well as variants in genes not previously linked to posterior segment uveitis. Based on a ranked list and protein-protein-interaction network, missense variants in NOD-like receptor family genes (NOD2, NLRC4, NLRP3, and NLRP1), CAPN5, and TYK2 were characterized via structural modeling and in silico calculations to predict how specific variants might alter protein structure and function. The majority of analyzed variants were notably different from wild type. CONCLUSIONS:This study implicates new pathways and immune signaling proteins that may be associated with posterior segment uveitis susceptibility. A larger cohort and functional studies will help validate the pathogenicity of the mutations identified. In specific cases, whole exome sequencing can help diagnose non-syndromic uveitis patients harboring known variants for syndromic inflammatory diseases.

BACKGROUND:Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. METHODS:This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. FINDINGS:Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. INTERPRETATION:In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran. FUNDING:Alnylam Pharmaceuticals.

OBJECTIVE:Intraoperative neuromonitoring (IONM) techniques aim to identify and potentially prevent nerve injury during surgeries. Prior studies into the efficacy of recurrent laryngeal nerve (RLN) IONM convey mixed results, with some claiming equivalence between IONM and no monitoring at all. The goal of the current study was to compare continuous RLN monitoring using the laryngeal adductor reflex (LAR) to intermittent RLN monitoring (intermittent IONM) to determine whether continuous monitoring reduces the incidence of intraoperative RLN injury during neck endocrine surgeries. METHODS:In this observational, historical case-control study, a historical cohort of patients monitored with intermittent-IONM (group 1, n = 130) were compared to prospectively collected data from consecutive nerves-at-risk monitored continuously with the LAR (LAR-CIONM, group 2, n = 205), at a single center by a single surgeon. The test benefit ratio and relative risk reduction (RRR) for LAR-CIONM over intermittent IONM were calculated. RESULTS:For group 1, nine nerves at risk exhibited intraoperative LOS with transient postoperative vocal fold (VF) hypomobility (n = 2) or immobility (VFI, n = 7). For group 2, two nerves at risk (0.98%) had sudden intraoperative LAR LOS following bipolar cautery, resulting in postoperative transient VFI (P = .004). In each group, there was one case of permanent postoperative VFI. The test benefit rate ratio for LAR-CIONM demonstrated a dramatic effect at 5.23, with an RRR of 81.0%. CONCLUSION/CONCLUSIONS:LAR-CIONM significantly decreased rates of postoperative transient VF paralysis and paresis over intermittent IONM alone (P = .004). Surgeons should be aware of the benefits and limitations of intermittent IONM versus CIONM. Intermittent IONM, although useful in nerve mapping and intraoperative decision making, has minimal benefit for the prevention of nerve injury, whereas CIONM can potentially reduce nerve injury rates and improve patient outcomes. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2020.

The IOC has proposed standard methods for recording and reporting of data for injury and illness in sport. The IOC consensus statement authors anticipated that sport-specific statements would provide further recommendations. This statement is the tennis-specific extension of the partner IOC statement. The International Tennis Federation Sport Science and Medicine Committee, in collaboration with selected external experts, met in June 2019 to consider athlete health monitoring issues specific to tennis. Once the IOC consensus statement was finalised, the tennis-specific consensus was drafted and agreed on by the members over three iterations. Compared with the IOC consensus statement, the tennis consensus contains tennis-specific information on injury mechanism, mode of onset, injury classification, injury duration, capturing and reporting exposure, reporting risk and study population. Our recommendations apply to able-bodied as well as wheelchair tennis players. Where applicable, specific recommendations are made for wheelchair tennis.

BACKGROUND AND PURPOSE/OBJECTIVE:Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. MATERIALS AND METHODS/METHODS:This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. RESULTS:< .003). CONCLUSIONS:Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.

Background and Purpose/UNASSIGNED:Hospital 30-day readmissions in patients with primary neurological problems are not well characterized. We sought to determine patient characteristics associated with readmission across 3 different inpatient neurology services at New York University Langone Hospital. Methods/UNASSIGNED:We retrospectively reviewed all 30-day readmissions from the General Neurology, Epilepsy, and Stroke services at NYULH Brooklyn and Manhattan campuses from 2016-2017 and compared them to a random sample of non-readmitted neurology patients. We used univariate analyses to compare demographics, clinical characteristics, disease specific metrics, and discharge factors of non-readmitted and readmitted groups and binomial logistic regression to examine specific variables with adjustment for confounders. Results/UNASSIGNED:We included 284 patients with 30-day readmissions and 306 control patients without readmissions matched by discharge location and service. After adjusting for confounders, we found that the following factors were associated with increased readmission risk: a recent hospital encounter increased risk for all services, increased number of medications at discharge, intensive care unit stay, higher length of stay, and prior history of seizure for the General Neurology Service, increased number of medications at discharge for the Epilepsy Service, and active malignancy and higher discharge modified Rankin Scale score for the Stroke Service. Conclusion/UNASSIGNED:This study identifies potential risk factors for readmission in patients across multiple neurology services. Further research is needed to establish whether these risk factors hold across multiple institutions.

Objective: A recent clinical trial with 0.7mg/kg/day of fenfluramine (FFA) showed 62.3% (IC 95%: -47.7%; -72.8%; p<0.001) reduction in convulsive seizure frequency (CSF) compared to placebo. However, the impact of the disease on the patient and their caregivers may depend on other variables. This alternative analysis value the impact of other results.
Method(s): After a baseline period of 6 weeks patients with DS ages 2 to 18 years, was randomized to FFA 0.7 or 0.2mg/kg/day or placebo added. Time to new event (time required to experience the same number of crisis as in the reference period [TTE]) was analyzed. Intervals without crisis and number of days without crisis was analyzed too.
Result(s): 119 patients with DS receiving FFA 0.7mg/kg/day; FFA0.2mg/kg/day; or placebo. TTE was significantly longer in active groups. Placebo: 6 weeks, FFA 0.2mg/kg/day:8 weeks and FFA 0.7mg/kg/day: >12 weeks (p<0.001; ~60% of patients in the FFA 0.7mg/kg/day group never reached their baseline seizure count and were censored). The number of days without crisis was higher in groups treated with FFA: 33 and 20 days without additional crisis counted in the active groups. The longest average without crisis was higher with FFA 0.7mg/kg/day (25 days; p<0.001) and FFA 0.2mg/kg/day (15 days; Px0.035) than with placebo (9.5 days).
Conclusion(s): FFA extended TTE and provided significantly more days without crisis and longer periods without crisis than placebo. Our analysis can help assess the ability of a treatment to reduce the burden of seizures in patients with SD and their caregivers